Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation

被引：723
作者：
Brown, E
McKee, T
diTomaso, E
Pluen, A
Seed, B
Boucher, Y
Jain, RK [1 ]
机构：
[1] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Boston, MA 02114 USA
[4] MIT, Biol Engn Div, Cambridge, MA 02139 USA
[5] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PL, Lancs, England
来源：
NATURE MEDICINE | 2003年 / 9卷 / 06期
关键词：
D O I：
10.1038/nm879
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The content and structure of collagen is essential in governing the delivery of therapeutic molecules in tumors. Thus, simple histological staining of tumor tissue biopsies for collagen could be used to assess the accessibility of molecular therapeutics in tumors. Here we show that it is possible to optically image fibrillar collagen in tumors growing in mice using second-harmonic generation (SHG). Using this noninvasive technique, we estimated relative diffusive hindrance, quantified the dynamics of collagen modification after pharmacologic intervention and provided mechanistic insight into improved diffusive transport induced by the hormone relaxin. This technology could offer basic scientists and clinicians an enhanced ability to estimate the relative penetrabilities of molecular therapeutics.
引用
收藏
页码：796 / 800
页数：5
相关论文
共 20 条
[1]   Two-photon laser scanning microscopy of epithelial cell-modulated collagen density in engineered human lung tissue [J].
Agarwal, A ;
Coleno, ML ;
Wallace, VP ;
Wu, WY ;
Sun, CH ;
Tromberg, BJ ;
George, SC .
TISSUE ENGINEERING, 2001, 7 (02) :191-202
[2]   In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy [J].
Brown, EB ;
Campbell, RB ;
Tsuzuki, Y ;
Xu, L ;
Carmeliet, P ;
Fukumura, D ;
Jain, RK .
NATURE MEDICINE, 2001, 7 (07) :864-868
[3]  
BYLANDER JE, 1987, P SOC EXP BIOL MED, V185, P76
[4]   Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues [J].
Campagnola, PJ ;
Millard, AC ;
Terasaki, M ;
Hoppe, PE ;
Malone, CJ ;
Mohler, WA .
BIOPHYSICAL JOURNAL, 2002, 82 (01) :493-508
[5]   New functions for the matrix metalloproteinases in cancer progression [J].
Egeblad, M ;
Werb, Z .
NATURE REVIEWS CANCER, 2002, 2 (03) :161-174
[6]   There is binding of collagen IV to β1 integrin during early skin basement membrane assembly [J].
Fleischmajer, R ;
Perlish, JS ;
Macdonald, ED ;
Schechter, A ;
Murdoch, AD ;
Iozzo, RV ;
Yamada, Y .
MORPHOGENESIS: CELLULAR INTERACTIONS, 1998, 857 :212-227
[7]   CONNECTIVE-TISSUE POLARITY - OPTICAL 2ND-HARMONIC MICROSCOPY, CROSSED-BEAM SUMMATION, AND SMALL-ANGLE SCATTERING IN RAT-TAIL TENDON [J].
FREUND, I ;
DEUTSCH, M ;
SPRECHER, A .
BIOPHYSICAL JOURNAL, 1986, 50 (04) :693-712
[8]  
FRIEDEN EH, 1985, P SOC EXP BIOL MED, V180, P39
[9]   Fibroblast-collagen-matrix contraction: growth-factor signalling and mechanical loading [J].
Grinnell, F .
TRENDS IN CELL BIOLOGY, 2000, 10 (09) :362-365
[10]   A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals [J].
Helmchen, F ;
Fee, MS ;
Tank, DW ;
Denk, W .
NEURON, 2001, 31 (06) :903-912
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